NK cells have shown great potential as cellular therapies for malignant diseases. Follicular Lymphoma (FL) is an incurable lymphoma with a substantial risk of transforming into an aggressive non-Hodgkin lymphoma with a poor prognosis. The immunobiology of NK cells within FL patients remains unclear. In this study, we comprehensively define the phenotype and function of NK cells from FL patient peripheral blood (PBMC) to inform NK cell-based treatment strategies.

Upon comparing FL patient PBMCs to Healthy Donor (HD) PBMCs, FL patient NK cells express similar levels of NK cell activating and inhibitory receptors, contrasting with other malignancies. However, FL patient NK cells demonstrate a decrease in CD69 MFI and percentage (p<0.01), CD25, TRAIL, and CD127 MFI (p<0.05) and increase in CD62L percentage and LAG3 MFI compared to HD (p<0.05). FL patient CD56^bright NK cells demonstrate decreased CCR7 and CD25 MFI (p<0.05) and CD25 percentage (p<0.005).

NK cell function was tested by measuring degranulation and cytokine production after stimulation. FL patient NK cells demonstrate enhanced degranulation compared to HD upon co-culture with K562’s (p=0.0006) and Raji’s with or without anti-CD20 mAbs (p<0.05). FL patient CD56^dim NK cells harbor similar granzyme B as HD. FL patient and HD NK cells have similar cytokine production (IFNᵧ, TNFɑ, and MIP1ɑ).

Our study revealed that FL patient blood NK cells demonstrate enhanced degranulation in response to tumor compared to HD with equivalent cytokine production. They exhibit increased LAG3 expression providing a potential checkpoint inhibitor target. In contrast to other malignancies, FL patient blood NK cells have functional properties that can be harnessed for autologous NK cellular therapies.

We are currently performing scRNA-sequencing and CODEX spatial profiling and have identified NK cells in the parafollicular T cell region of FL lymph nodes. We aim to define interactions of NK cells within the FL microenvironment.